Bottom Line:
Although APP is expressed in several tissues outside the human central nervous system, the functions of APP and its family members in other tissues are still poorly understood.We analyzed several topological properties of the APP interaction network and the biological and physiological properties of the proteins in the APP interaction network were also specified by gene ontologyand pathways analyses.Our approach allowed the identification of novel interactions and recognition of key APP interacting proteins for male reproduction, particularly in sperm-oocyte interaction.

Background: Amyloid precursor protein (APP) is widely recognized for playing a central role in Alzheimer's disease pathogenesis. Although APP is expressed in several tissues outside the human central nervous system, the functions of APP and its family members in other tissues are still poorly understood. APP is involved in several biological functions which might be potentially important for male fertility, such as cell adhesion, cell motility, signaling, and apoptosis. Furthermore, APP superfamily members are known to be associated with fertility. Knowledge on the protein networks of APP in human testis and spermatozoa will shed light on the function of APP in the male reproductive system.

Results: We performed a Yeast Two-Hybrid screen and a database search to study the interaction network of APP in human testis and sperm. To gain insights into the role of APP superfamily members in fertility, the study was extended to APP-like protein 2 (APLP2). We analyzed several topological properties of the APP interaction network and the biological and physiological properties of the proteins in the APP interaction network were also specified by gene ontologyand pathways analyses. We classified significant features related to the human male reproduction for the APP interacting proteins and identified modules of proteins with similar functional roles which may show cooperative behavior for male fertility.

Conclusions: The present work provides the first report on the APP interactome in human testis. Our approach allowed the identification of novel interactions and recognition of key APP interacting proteins for male reproduction, particularly in sperm-oocyte interaction.

Mentions:
First, we focused on local interactions of APP/APLP2, that is, the first direct interactors of APP/APLP2 and interactions between them. We identified 455 proteins connected to APP (Methods) including the partners identified by YTH (Figure 3a). All the proteins in the YTH data were newly found as interactors of APP except RANBP9, which was previously published as an APP interactor [9]. The absence of protein overlapping may be due to the fact that the YTH was performed using a library from human testis and the previous APP interactors were mainly identified in neuronal tissues. Indeed, published data indicate that 4% of the mammalian genome (more than 2,300 genes) encodes genes specifically expressed in the male germ line during or after the completion of spermatogenesis [39]. Regarding APLP2, we identified 6 proteins (including APP) as its interactors from the DBs which were highly specific to or strongly expressed in testis. In total, 1,803 interactions were identified between 457 proteins including APP and APLP2. Only one protein (BRCA1) among the nearest neighbors of APLP2 was not directly connected to APP which may reflect an isoform-specific role for APLP2.Figure 3

Mentions:
First, we focused on local interactions of APP/APLP2, that is, the first direct interactors of APP/APLP2 and interactions between them. We identified 455 proteins connected to APP (Methods) including the partners identified by YTH (Figure 3a). All the proteins in the YTH data were newly found as interactors of APP except RANBP9, which was previously published as an APP interactor [9]. The absence of protein overlapping may be due to the fact that the YTH was performed using a library from human testis and the previous APP interactors were mainly identified in neuronal tissues. Indeed, published data indicate that 4% of the mammalian genome (more than 2,300 genes) encodes genes specifically expressed in the male germ line during or after the completion of spermatogenesis [39]. Regarding APLP2, we identified 6 proteins (including APP) as its interactors from the DBs which were highly specific to or strongly expressed in testis. In total, 1,803 interactions were identified between 457 proteins including APP and APLP2. Only one protein (BRCA1) among the nearest neighbors of APLP2 was not directly connected to APP which may reflect an isoform-specific role for APLP2.Figure 3

Bottom Line:
Although APP is expressed in several tissues outside the human central nervous system, the functions of APP and its family members in other tissues are still poorly understood.We analyzed several topological properties of the APP interaction network and the biological and physiological properties of the proteins in the APP interaction network were also specified by gene ontologyand pathways analyses.Our approach allowed the identification of novel interactions and recognition of key APP interacting proteins for male reproduction, particularly in sperm-oocyte interaction.

Background: Amyloid precursor protein (APP) is widely recognized for playing a central role in Alzheimer's disease pathogenesis. Although APP is expressed in several tissues outside the human central nervous system, the functions of APP and its family members in other tissues are still poorly understood. APP is involved in several biological functions which might be potentially important for male fertility, such as cell adhesion, cell motility, signaling, and apoptosis. Furthermore, APP superfamily members are known to be associated with fertility. Knowledge on the protein networks of APP in human testis and spermatozoa will shed light on the function of APP in the male reproductive system.

Results: We performed a Yeast Two-Hybrid screen and a database search to study the interaction network of APP in human testis and sperm. To gain insights into the role of APP superfamily members in fertility, the study was extended to APP-like protein 2 (APLP2). We analyzed several topological properties of the APP interaction network and the biological and physiological properties of the proteins in the APP interaction network were also specified by gene ontologyand pathways analyses. We classified significant features related to the human male reproduction for the APP interacting proteins and identified modules of proteins with similar functional roles which may show cooperative behavior for male fertility.

Conclusions: The present work provides the first report on the APP interactome in human testis. Our approach allowed the identification of novel interactions and recognition of key APP interacting proteins for male reproduction, particularly in sperm-oocyte interaction.